DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1900
APPENDIX II
DESIGN AND OPTIMIZATION OF DOSAGE REGIMENS: PHARMACOKINETIC DATA
Table AII–1
Pharmacokinetic Data (Continued)
BIOAVAILABILITY URINARY BOUND IN CLEARANCE VOL. DIST. HALF-LIFE PEAK TIME PEAK
(ORAL) (%) EXCRETION (%) PLASMA (%) (mL/min/kg) (L/kg) (hours) (hours) CONCENTRATION
Acyclovir
15-30 a 75 ± 10 15 ± 4 CL = 3.37CL cr
+ 0.69 ± 0.19 2.4 ± 0.7 1.5-2 b 3.5-5.4 μM b
0.41
b Neo a Neo a RD, Neo
i Child i RD i Child
a
Decreases with increasing dose. b Range of steady-state concentrations following a 400-mg
dose given orally every 4 hours to steady state.
Albendazole a
— b <1 70 10.5-30.7 c — 8 (6-15) d 2-4 e 0.50-1.8 μg/mL e
a Food
a
Oral albendazole undergoes rapid and essentially complete first-pass metabolism to albendazole
sulfoxide (ALBSO), which is pharmacologically active. Pharmacokinetic data for ALBSO
in male and female adults are reported. b The absolute bioavailability of ALBSO is not known
but is increased by high-fat meals. c CL/F following twice-daily oral dosing to steady state.
Chronic albendazole treatment appears to induce the metabolism of ALBSO. d t 1/2
reportedly
shorter in children with neurocysticercosis compared with adults; may need to be dosed more
frequently (three times a day) in children, rather than twice a day, as in adults. e Following a
7.5-mg/kg oral dose given twice daily for 8 days to adults.
Albuterol a
Reference: Laskin OL. Clinical pharmacokinetics of acyclovir. Clin Pharmacokinet, 1983,
8:187–201.
References: Marques MP, et al. Enantioselective kinetic disposition of albendazole sulfoxide
in patients with neurocysticercosis. Chirality, 1999, 11:218–223. PDR58, 2004, p. 1422.
Sanchez M, et al. Pharmacokinetic comparison of two albendazole dosage regimens in
patients with neurocysticercosis. Clin Neuropharmacol, 1993, 76:77–82. Sotelo J, et al.
Pharmacokinetic optimisation of the treatment of neurocysticercosis. Clin Pharmacokinet,
1998, 34:503–515.
PO, R: 30 ± 7 R: 46 ± 8 Rac: 7 ± 1 R: 10.3 ± 3.0 R: 2.00 ± 0.49 R: 2.00 ± 0.49 R: 1.5 c R: 3.6 (1.9-5.9)
PO, S: 71 ± 9 S: 55 ± 11 S: 6.5 ± 2.0 S: 1.77 ± 0.69 S: 2.85 ± 0.85 S: 2.0 c ng/mL c
IH, R: 25 b RD b b RD b S: 11.4 (7.1-16.2)
IH, S: 47
ng/mL c
a
Data from healthy subjects for R- and S-enantiomers. No major gender differences. No
kinetic differences in asthmatics. β-Adrenergic activity resides primarily with R-enantiomer.
PO, oral; IH, inhalation. Oral dose undergoes extensive first-pass sulfation at the intestinal
mucosa. b CL/F reduced, moderate renal impairment. c Median (range) following a single 4-mg
oral dose of racemic-albuterol.
References: Boulton DW, et al. Enantioselective disposition of albuterol in humans. Clin Rev
Allergy Immunol, 1996, 14:115–138. Mohamed MH, et al. Effects of gender and race on
albuterol pharmacokinetics. Pharmacotherapy, 1999, 19:157–161.